SCIENCE@home

ABSTRACT

Adding to the cross-presentation family Immune responses to viral or tumor antigens are typically initiated by the process of cross-presentation. Cross-presentation is believed to be the major way that innate immune cells, such as the classical dendritic cell 1 (cDC1) subset, activate and prime immunological T cells. Theisen et al. used CRISPR-based screening to identify regulators of cross-presentation by cDC1s (see the Perspective by Barbet and Blander). One such regulator that was identified, WDFY4 (WD repeat- and FYVE domain–containing protein 4), was required for cross-presentation of cell- and bacterial-associated antigens. WDFY4 played a critical role in cDC1-mediated viral and tumor immunity yet did not seem necessary for major histocompatibility complex class II presentation or for cross-presentation by monocyte-derived DCs. Science, this issue p. 694; see also p. 641 Dendritic cells require WDFY4 for cross-presentation. During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8+ T cells by Batf3-dependent CD8α+/XCR1+ classical dendritic cells (cDC1s). We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain–containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. However, WDFY4 was not required for major histocompatibility complex class II presentation, nor for cross-presentation by monocyte-derived dendritic cells. In contrast to Batf3–/– mice, Wdfy4–/– mice displayed normal lymphoid and nonlymphoid cDC1 populations that produce interleukin-12 and protect against Toxoplasma gondii infection. However, similar to Batf3–/– mice, Wdfy4–/– mice failed to prime virus-specific CD8+ T cells in vivo or induce tumor rejection, revealing a critical role for cross-presentation in antiviral and antitumor immunity.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-87 of 87 references · Page 1 of 1

CITED BY

Showing 1-100 of 293 citing papers · Page 1 of 3

123
Next